Objective Morphogens are locally produced molecules that act over long distances in tissues to control the pattern of gene expression. A particularly well-understood model system for studying the mechanisms of morphogen-mediated patterning is the vertebrate neural tube. Here, Sonic Hedgehog (Shh) induces discrete neuronal progenitor domains through regulation of a combinatorial code of transcription factors. The observed precision and reproducibility of gene expression appears greater than can be accounted for by the precision of Shh signalling alone. Thus, mechanisms must exist that filter signaling noise. We hypothesize that this involves either the properties of the downstream transcriptional network regulated by Shh signaling or active cell sorting.The proposed research project aims at quantifying the amount of noise in the pattern of gene expression in the vertebrate neural tube, and investigating how, at which level, and to which extent this noise is buffered. To achieve this goal, I will generate fluorescent reporters for the expression of three key Shh target genes, Nkx2.2 Olig2 and Pax6, and spatiotemporally correlate the activity of these reporters with Shh pathway activity. In parallel, a quantitative analysis of the behaviour of cells will be performed to elucidate the contribution of differential cell adhesion and active cell sorting. The combined results will be integrated into a theoretical framework to account qualitatively and quantitatively for Shh-mediated patterning of the neural tube.Due to the iterative deployment of Hedgehog (Hh) signalling during animal development and the evolutionary conservation of the Hh pathway, the types of mechanisms deduced from our quantitative analysis will probably not only apply to Shh-mediated patterning in the neural tube, but to a broad range Hh-mediated patterning processes. Furthermore, similar mechanisms of noise compensation may be also deployed by other morphogen systems. Fields of science natural sciencesbiological sciencesgeneticsnatural sciencesbiological sciencesmolecular biologymolecular geneticsnatural sciencesbiological sciencescell biologycell signaling Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2013-IEF - Marie-Curie Action: "Intra-European fellowships for career development" Call for proposal FP7-PEOPLE-2013-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator THE FRANCIS CRICK INSTITUTE LIMITED EU contribution € 231 283,20 Address 1 MIDLAND ROAD NW1 1AT London United Kingdom See on map Region London Inner London — West Camden and City of London Activity type Research Organisations Administrative Contact Heather Woods (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Participants (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all MEDICAL RESEARCH COUNCIL Participation ended United Kingdom EU contribution No data Address 20 Park Crescent W1B 1AL LONDON See on map Activity type Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments) Administrative Contact David Jones (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data